Contraception method using competitive progesterone antagonists and novel compounds useful therein

Abstract

Competitive progesterone antagonists, including two novel steroids, viz., 11β,19-[4-(cyanophenyl)-o-phenylene]-17β-hydroxy-17α-(3-hydroxyprop-1(Z)-enyl)-4-androsten-3-one and 11β,19-[4-(3-pyridinyl)-o-phenylene]-17β-hydroxy-17α-(3-hydroxyprop-1(Z)-enyl)-4-androsten-3-one, inhibit formation of endometrial glands at below their ovulation inhibiting dose and the abortive dose, and thus achieve oral contraception in females without adversely affecting the menstrual cycle and without risk of aborting a previous implanted fertilized egg or a fetus.

What is claimed is: 
     
       1. A method of contraception in a female, which comprises administering to the female during the follicular phase of her menstrual cycle and optionally also in the luteal phase thereof an amount of a competitive progesterone antagonist, which is less than an ovulation-inhibiting dose and less than an abortion-inducing dose and which is effective to inhibit the formation of endometrial glands and epithelium growth. 
     
     
       2. A method according to claim 1, wherein the competitive progesterone antagonist is administered during both the follicular phase and the luteal phase. 
     
     
       3. A method according to claim 2, wherein the progesterone antagonist is administered orally about once weekly during each week of the menstrual cycle. 
     
     
       4. A method according to claim 1, wherein the competitive progesterone antagonist is 11β-[(4-N,N-Dimethylamino)-phenyl]-17β-hydroxy-17α-propinyl-4,9(10)-estradien-3-one (RU 38486),   11β-[(4-N,N-dimethylamino)-phenyl]-17β-hydroxy-18-methyl-17.alpha.-propinyl-4,9(10)-estradien-3-one,   11β-[(4-N,N-dimethylamino)-phenyl]-17aβ-hydroxy-17aα-propinyl-D-homo-4,9(10),16-estratrien-3-one,   1β -p-methoxyphenyl-17β-hydroxy-17α-ethinyl-4,9(10)-estradien-3-one, or   11β-(4-acetylphenyl)-17β-hydroxy-17α-(prop-1-inyl)-4,9(10)-estradien-3-one.   
     
     
       5. A method according to claim 1, wherein the competitive progesterone antagonist is 11β-(4-Dimethylaminophenyl)-17α-hydroxy-17β-(3-hydroxypropyl)-13α-methyl-4,9-gonadien-3-one, or   11β-(4-acetylphenyl)-17β-hydroxy-17α-(3-hydroxyprop-1-enyl)-4,9(10)-estradien-3-one.   
     
     
       6. A method according to claim 1, wherein the competitive progesterone antagonist is 11β,19-[4-(cyanophenyl)-o-phenylene]-17β-hydroxy-17α-(3-hydroxyprop-1(Z)-enyl)-4-androsten-3-one, or   11β,19-[4-(3-pyridinyl)-o-phenylene]-17β-hydroxy-17α-(3-hydroxyprop-1(Z)-enyl)-4-androsten-3-one.   
     
     
       7. A method according to claim 1, wherein the progesterone antagonist is administered in individual dosage units every 4 to every 10 days, beginning on any day before the day of ovulation of the first menstrual cycle during which the administration occurs. 
     
     
       8. A method according to claim 1, wherein the progesterone antagonist is administered orally. 
     
     
       9. A method according to claim 1, wherein the female is a human being. 
     
     
       10. A method according to claim 1, wherein the female is a human being and the progesterone antagonist is administered thereto orally every week of each menstrual cycle during which contraception is desired. 
     
     
       11. A method according to claim 10, wherein the competitive progesterone antagonist is 11β,19-[4-(cyanophenyl)-o-phenylene]-17β-hydroxy-17α-(3-hydroxyprop-1(Z)-enyl)-4-androsten-3-one, or   11β,19-[4-(3-pyridinyl)-o-phenylene]-17β-hydroxy-17α-(3-hydroxyprop-1(Z)-enyl)-4-androsten-3-one.   
     
     
       12. An 11β,19-[4-(cyanophenyl)-o-phenylene] or 11β,19-[4-(3-pyridinyl)-o-phenylene]-17β-hydroxy-17α-(3-hydroxyprop-1(Z)-enyl)-4-androsten-3-one of the formula ##STR3## wherein R is ##STR4## 
     
     
       13. 11β,19-[4-(cyanophenyl)-o-phenylene]-17β-hydroxy-17α-(3-hydroxyprop-1(Z) -enyl)-4-androsten-3-one, a compound of claim 12. 
     
     
       14. 11β,19-[4-(3-pyridinyl)-o-phenylene]-17β-hydroxy-17.alpha.-(3-hydroxyprop-1(Z)-enyl)-4-androsten-3-one, a compound of claim 12. 
     
     
       15. The method of claim 1, wherein the female is a human being and the dose amount is 0.25 to 50 mg per administration. 
     
     
       16. The method of claim 7, wherein the female is a human being and the dose amount is 0.25 to 50 mg per administration. 
     
     
       17. The method of claim 10, wherein the dose amount is 0.25 to 50 mg per administration.